PHRD5015 Lecture 18 (Ju) - Autoimmunity

unwanted immune response against self-tissue Ags that cause chronic inflammatory injury

• 1) CTLA4
• 2) IL-10
• 3) FasL

• activated T cells clear pathogen during infection, but then recognize something similar
• in the body that should be recognized as self

RA

• 1) T cell activation by unknown Ag's
• 2) initiation of inflammatory response
• 3) cytokine production, synovial inflammation

• known association of RA w/ MHC II Ag's
• large # CD4+ T cells in RA synovium

while T cells may be important in initiating disease, chronic inflammation is perpetuated by macrophages and fibroblasts though T cell INDEPENDENT manner

• secreted by macrophages
• maintain synovial fibroblast in an activated state

same as IL-1 fcn -> maintain synovial fibroblast in activated state

• secreted by fibroblasts
• promotes maturation of newly recruited monocytes to macrophages

• produced by both macrophages & fibroblasts
• stimulates B cell maturation to plasma cell

• secreted by fibroblasts
• recruit neutrophils to site

systemic lupus erythematosus

• 1) renal
• 2) vasculitis
• 3) CNS

• 1) ssDNA
• 2) dsDNA
• 3) histone
• 4) chromatins

Type III (immune-complex-mediated)

insulin dependent diabetes mellitus

multiple sclerosis

• 1) inhibit leukocyte proliferation
• 2) inhibit Ag presentation
• 3) inhibit T-cell migration across BBB
• 4) modulate cytokine production

anti-4 integrin mAb binds VLA-4 to mediate CNS migration of lymphocytes

• 1) DNA crosslinks/breaks; inhibit DNA repair
• 2) cytocidal effect 
• 3) inhibits B/T cell & macrophage proliferation 4) impair Ag presentation

peptide tetramer (GLATiramer) resembling protein found on myelin that diverts autoimmune response away from myelin

downregulates S1P1 expression on activated T cells to decrease gradient -> cells unresponsive & unable to migrate out of lymph nodes -> reduced lymphocytes in CNS

• 1) inhibits pyrimidine synthesis
• 2) reduces # activated lymphocytes in CNS

• 1) small molecule w/ anti-inflammatory properties
• 2) prevent Tcell infiltration to CNS
• 3) affect Ag presentation